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General pathology · Neoplasia

Invasion and metastasis: the metastatic cascade, step by step !

  • Process

To spread, a cancer cell must let go of its neighbours, break through tissue, travel in vessels and grow in a new organ. Few cells manage all of it.

Updated 2026-11-01

What it is

Metastasis is the spread of tumour cells to sites discontinuous with the primary, and it causes most cancer deaths. It is a multistep cascade: detachment, invasion of the extracellular matrix, entry into vessels, survival in the circulation, exit at a distant site and growth there. The process is inefficient: most circulating tumour cells die, which is why the few successful clones have special traits.

Function

  • Proteolysis also releases growth factors stored in the matrix, which further feeds the tumour.
  • Tumour-associated macrophages and fibroblasts help invasion by producing proteases and growth factors.
  • Chemokine receptors on tumour cells, matched to chemokines in certain organs, partly explain organ preference.

Step by step

  1. Carcinoma cells lose E-cadherin and detach from their neighbours.
  2. They secrete proteases (matrix metalloproteinases, cathepsins) that break down the basement membrane.
  3. New adhesion molecules (integrins, laminin receptors) let them grip and move through the matrix.
  4. They migrate, guided by motility factors and by fragments of the broken matrix.
  5. They enter lymphatics or small vessels (intravasation).
  6. In the blood many die; survivors clump with platelets and evade immune attack.
  7. They adhere to the endothelium of a distant organ and exit the vessel (extravasation).
  8. In the new site they may stay dormant for years or grow into a metastasis once they recruit vessels.

Clinical notes

  • Most patients with cancer die of metastases, not of the primary tumour.
  • Microscopic metastases may already exist at diagnosis, the rationale for adjuvant therapy after surgery.
  • A carcinoma of unknown primary is metastatic disease whose primary site stays hidden.
  • Late recurrence (for example breast cancer years after surgery) reflects dormant disseminated cells.

Test yourself

Think of the answer, then tap the question to see it.

Which adhesion molecule is lost early in carcinoma invasion?

E-cadherin, which normally holds epithelial cells together.

Which enzymes allow tumour cells to cross the basement membrane?

Matrix metalloproteinases, such as type IV collagenases, and other proteases like cathepsins.

What does the seed and soil idea explain?

That metastases grow where the organ's environment (receptors, chemokines, growth factors) suits the tumour cell, not just where blood flow takes it.

Why is metastasis called inefficient?

Millions of cells may enter the blood, but most die from shear forces, loss of anchorage or immune attack; only rare clones form metastases.

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: Metastatic Cancer: When Cancer Spreads (National Cancer Institute (NCI), 2026); What Is Cancer? (National Cancer Institute (NCI), 2026); Angiogenesis Inhibitors (National Cancer Institute (NCI), 2026).

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Representative model, for educational purposes only.